The antimicrobial peptide, lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo

International Journal of Cancer - Tập 119 Số 3 - Trang 493-500 - 2006
Liv Tone Eliassen1, Gerd Marit Berge1, Arild Leknessund2, Mari Wikman1, Inger Lindin1, Cecilie Løkke2, Frida Ponthan3, John Inge Johnsen3, Baldur Sveinbjørnsson4, Per Kogner3, Trond Flægstad2, Øystein Rekdal1
1Department of Biochemistry, Faculty of Medicine, University of Tromsø, Tromsø, Norway
2Department of Pediatrics, Faculty of Medicine, University of Tromsø, Tromsø, Norway
3Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden,
4Department of Experimental Pathology, Faculty of Medicine, University of Tromso, Tromso, Norway

Tóm tắt

AbstractAntimicrobial peptides have been shown to exert cytotoxic activity towards cancer cells through their ability to interact with negatively charged cell membranes. In this study the cytotoxic effect of the antimicrobial peptide, LfcinB was tested in a panel of human neuroblastoma cell lines. LfcinB displayed a selective cytotoxic activity against both MYCN‐amplified and non‐MYCN‐amplified cell lines. Non‐transformed fibroblasts were not substantially affected by LfcinB. Treatment of neuroblastoma cells with LfcinB induced rapid destabilization of the cytoplasmic membrane and formation of membrane blebs. Depolarization of the mitochondria membranes and irreversible changes in the mitochondria morphology was also evident. Immuno‐ and fluorescence‐labeled LfcinB revealed that the peptide co‐localized with mitochondria. Furthermore, treatment of neuroblastoma cells with LfcinB induced cleavage of caspase‐6, ‐7 and ‐9 followed by cell death. However, neither addition of the pan‐caspase inhibitor, zVAD‐fmk, or specific caspase inhibitors could reverse the cytotoxic effect induced by LfcinB. Treatment of established SH‐SY‐5Y neuroblastoma xenografts with repeated injections of LfcinB resulted in significant tumor growth inhibition. These results revealed a selective destabilizing effect of LfcinB on two important targets in the neuroblastoma cells, the cytoplasmic‐ and the mitochondria membrane. © 2006 Wiley‐Liss, Inc.

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Thông tin xuất bản

International Journal of Cancer

Tập 119 Số 3

493-500

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